R Aneja

Usefulness of anti -CCP antibodies in rheumatic diseases in Indian patients.

BACKGROUND The usefulness of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) to identify rheumatic arthritis (RA) from other rheumatic diseases presenting with joint pain is not well studied. AIMS We aimed to determine the sensitivity and specificity of anti-CCP antibodies in Indian RA patients with respect to non-RA rheumatic diseases and to study the relationship of anti-CCP antibodies and IgG, IgM and IgA rheumatoid factor in RA. SETTINGS AND DESIGN Case-control cross-sectional study carried out in the rheumatology division of All India Institute of Medical Sciences. MATERIALS AND METHODS Sixty-three patients with rheumatoid arthritis (RA) and 51 patients with non-RA rheumatic diseases having joint pain were included in the study. Sera were tested for anti-CCP antibodies (IgG) and IgA, IgM, IgG rheumatoid factor, using a commercially available enzyme-linked immunosorbent assay. STATISTICAL ANALYSIS Statistical analysis was performed using SPSS statistical software version 11.5. RESULTS Fifty-four of 63 RA patients (85.71%) were positive for anti-CCP antibodies. In the non-RA group, anti-CCP antibody was positive in only 5 of 51 patients (9.8%). Our study found a sensitivity of 85% and a specificity of 90.19% with regard to the use of anti-CCP antibodies assay in patients with joint pain to correctly identify RA. Anti-CCP antibodies positive patients did not have more erosive disease. IgM-RF-positive patients had more erosion when compared to the IgM-RF-negative group. Thirty-two of 57 (56.1%) IgM-RF-positive patients had erosions, while no patient (0/6 patients) had erosions in the IgM-RF-negative group (P=0.01) CONCLUSION Anti-CCP antibodies have high sensitivity and specificity for diagnosis of RA, in Indian patients. Anti-CCP antibodies positive patients did not have more erosive disease in our study.

Prevalence of peripheral neuropathy in patients with newly diagnosed rheumatoid arthritis

Abstract Objective To look for the frequency and pattern of neuropathy in Indian patients with rheumatoid arthritis (RA). Patients and Methods One hundred newly diagnosed patients with RA (ACR 1987 revised criteria) visiting our hospital, over a period of 3 years were screened. Diabetics, outstation patients, chronic alcoholics, those with any known cause for peripheral neuropathy and patients having an overlap with the other rheumatological illness were excluded. Clinical assessment included detailed history and examination with special reference to extra-articular features and neuropathy with relevant clinical parameters like tender joint count, swollen joint count, etc. Routine laboratory investigations and autoantibodies (RF, ANA, anti-CCP) were obtained on all patients. All the patients with or without clinical manifestations of neuropathy underwent nerve conduction studies. Autonomic function studies were performed in selected patients. Results Subjects included 66 patients (M 13:F 53) with mean age of 42 (±13.42) years and median disease duration of 36 months (IQR-13.5, 60). Sensory symptoms were present in 9 patients (13.6%). None had motor symptoms. On neurological examination, 16 patients had sensory (24.2%) and 6 (9.09%) had motor abnormalities. Nerve conduction studies showed abnormality in 25 patients (37.87%). Evidence of entrapment neuropathy was found in 6 patients (9.09%; 5 patients with median nerve involvement [unilateral, 3 and bilateral, 2] and 1 patient with unilateral ulnar nerve involvement), 3 patients had only sensory neuropathy, 5 had mixed sensory motor and 3 had only motor neuropathy. Eight patients (12.12%) had only small fibre neuropathy as detected by sympathetic skin response and quantitative sensory testing. Conclusion This study shows high prevalence of subclinical neuropathy in Indian patients with RA. This may be an important contributor to disability.

DAS 28 for defining remission in rheumatoid arthritis in Indian patients

Abstract Objective To establish DAS 28 and DAS 28-3 scores that best define remission in Indian patients with rheumatoid arthritis (RA). Patients and Methods All patients diagnosed with RA visiting AIIMS, New Delhi over a period of 3 months were recruited. Clinical assessment included 28 joint counts for swelling and tenderness, duration of early morning stiffness, patient global assessment of disease activity, fatigue, joint pains and ESR. DAS 28 and DAS 28-3 scores were calculated and receiver operating characteristics curve analysis was performed to define cutoff values utilizing ‘ACR 5/6’ and ‘ACR 4/5’ remission criteria. Results Subjects included 207 patients (M: 44; F: 163) with mean age of 47.4 ± 12.6 years, median disease duration of 8 [4.12–14] years.‘ACR 5/6’ and ‘ACR 4/5’ criteria for remission were satisfied by 34 (16.42%) and 44 patients (21.25%) patients, respectively. DAS 28 score of 2.94 (sensitivity 84.4%, specificity 85.3%) and DAS 28-3 score of 3.02 (sensitivity 82.1%, specificity 82.4) best defined the ‘ACR 5/6’ remission. Corresponding values using ‘ACR 4/5’ remission were 3.04 (sensitivity 85.9%, specificity 84.1%) for DAS 28 and 3.05 (sensitivity 82.2%, specificity 81.8%) for DAS 28-3. Conclusions A cutoff value

Assessment of serum nitrite as biomarker of disease activity in ankylosing spondylitis

Abstract Background The assessment of disease activity in patients with ankylosing spondylitis (AS) continues to be a challenging issue. The currently available markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) show poor correlation with clinical disease activity. There is a need for good biomarkers to assess disease activity. We explored serum nitrite, a stable end product of metabolism of NO, which is known to rise in inflammation, as a potential biomarker of disease activity in AS. Objectives To compare the levels of serum nitrite between patients with AS and healthy controls and to correlate levels of serum nitrite with disease activity in four assessment in ankylosing spondylitis (ASAS) domains. Methods Fifty patients satisfying modified New York criteria for AS were recruited for the study. Patients were assessed in the following ASAS domains: physical function (BASFI), pain (VAS, 0–100), patient global assessment (VAS, 0–100) and inflammation (mean of the two morning stiffness related BASDAI scores). Eighty-seven healthy controls were also included for comparison. Blood samples (12 hours fasting) were obtained and stored for serum nitrite level estimation, which was done by Dings method. The median levels of serum nitrite were compared between the two groups. Correlation of serum nitrite levels was sought with individual domains of disease activity. Results The median serum nitrite levels in patients with AS were markedly elevated as compared to those in controls (39 μmol/L [IQR 27–50] vs. 4.75 μmol/L [2.53–12], P = 0.001 (Mann-Whitney U test). There was only one patient whose serum nitrite level overlapped with that of controls. Clinical assessment of disease activity (individual ASAS domains-physical function (BASFI), pain, patient global assessment and inflammation (mean of the two morning stiffness) did not show a good correlation with serum nitrite levels. Conclusions Serum nitrite level was increased eight folds in patients with AS when compared with controls. Thus its measurement holds promise in differentiating between inflammatory and mechanical low back pain. However, there was no variation across a range of levels of disease activity making it unsuitable as a biomarker to monitor disease activity in AS.

Efficacy of oral pilocarpine in patients with Sjøgren's syndrome

Abstract Introduction A number of drugs have been tried for the relief of sicca symptoms in Sjogrens syndrome (SS) without much benefit. Lately, oral pilocarpine, a muscarinic cholinergic agent, has been reported to be useful. Objective To document the effect of oral pilocarpine on sicca symptoms in patients with SS. Patients and Methods The study group comprised 41 patients (4 men and 37 women) diagnosed as SS (primary or secondary) according to European criteria. Patients were recruited from the rheumatology clinic, cornea clinic, and medicine OPD of AIIMS between April 2003 and March 2005. Study subjects received oral pilocarpine, 5 mg thrice a day for a total duration of 12 weeks. Assessment included measurement of salivary flow, Schirmers test, Rose Bengal staining of cornea and slit lamp examination at 0, 6, and 12 weeks. Measurement of salivary flow and Schirmers test was performed twice at every visit, pre-dose and post-dose. All the patients underwent subjective self-assessment of sicca symptoms on visual analogue scale (VAS). Statistical analysis was carried out using paired t-test and repeated measure analysis of variance. Results The mean age was 52.61 ±9.14 years. Mean duration of dry eye and dry mouth symptoms were 52.02 and 42.51 months, respectively. Treatment with pilocarpine was associated with a significant decrease in the VAS score for dry mouth and dry eye symptoms. Statistically significant increase in salivary flow rate was noticed after the first dose of pilocarpine and was maintained for 12 weeks. Rose Bengal score showed a significant improvement even though Schirmers test result did not show improvement. The most common side effect was sweating. No serious side effect was noticed. Conclusions Treatment of sicca symptoms of SS with oral pilocarpine was found to be safe and efficacious.

Complex regional pain syndrome—management options

Abstract The natural history of Complex Regional Pain Syndrome (CRPS) is not well understood and the progression varies between different patients. The pathogenesis of this disorder is not well understood and a single mechanism can barely account for all the changes that are seen. In the absence of any pathognomonic sign or investigation, the diagnosis is suggested by the presence of constellation of symptoms, signs and laboratory findings. It is often under-diagnosed and undertreated resulting in significant morbidity and impaired quality of life. The crux of management lies in formulating a multidisciplinary planned approach based on the principles of chronic pain management, rehabilitation and psychotherapy with physiotherapy playing a very important role. Corticosteroids might be useful in a select group of patients in the early stages. Long-term use is not recommended as it has a questionable risk-benefit ratio. A number of new drugs are being tried that include thalidomide, calcium channel blockers, free radical scavengers, oral sympatholytic drugs, and clonidine. Encouraging results have been seen with bisphosphonates. Lenalinomide and neurotropin are other newer agents undergoing evaluation for efficacy in CRPS. Owing to lack of proper understanding of the pathogenesis and lack of animal models, current treatment for CRPS is essentially symptomatic and suboptimal. This paper attempts to review the role of various therapeutic modalities in the management of CRPS with emphasis on the emerging therapies.

B cell therapy in rheumatology: current perspectives

In the recent years there has been a steady increase in the armamentarium of drugs that are available with the rheumatologists. More and more targeted therapies are reaching the clinic. This is a reflection of the improvement in understanding of the immunological basis of autoimmune disorders and availability of technologies to make targeted therapies. The role of B cells in perpetuating and maintaining immune responses is now better understood. This has triggered research into the development of biologics specifically targeting the B Cells. The latest drug that has reached the clinic is rituximab, a chimeric monoclonal antibody to the CD20 molecule on the surface of mature B cells. It has been approved for management of patients with moderate to severe rheumatoid arthritis (RA) in adults who have had inadequate response to one or more biologic therapies. The success of rituximab therapy is a proof of the fundamental role of B cells in autoimmunity. B cell targeted therapies are here to stay and many more agents targeting various aspects of B cell biology are under development. This article discusses the current concepts of B cell biology and how the B cells can be targeted. It also reviews the emerging therapeutic agents targeting B cells with special reference to the trials that lead to approval of rituximab for RA.